No turning, a mouse mutation causing left-right and axial patterning defects.
Patterning along the left/right axes helps establish the orientation of visceral organ asymmetries, a process which is of fundamental importance to the viability of an organism. A linkage between left/right and axial patterning is indicated by the finding that a number of genes involved in left/right patterning also play a role in anteroposterior and dorsoventral patterning. We have recovered a spontaneous mouse mutation causing left/right patterning defects together with defects in anteroposterior and dorsoventral patterning. This mutation is recessive lethal and was named no turning (nt) because the mutant embryos fail to undergo embryonic turning. nt embryos exhibit cranial neural tube closure defects and malformed somites and are caudally truncated. Development of the heart arrests at the looped heart tube stage, with cardiovascular defects indicated by ballooning of the pericardial sac and the pooling of blood in various regions of the embryo. Interestingly, in nt embryos, the direction of heart looping was randomized. Nodal and lefty, two genes that are normally expressed only in the left lateral plate mesoderm, show expression in the right and left lateral plate mesoderm. Lefty, which is normally also expressed in the floorplate, is not found in the prospective floor plate of nt embryos. This suggests the possibility of notochordal defects. This was confirmed by histological analysis and the examination of sonic hedgehog, Brachyury, and HNF-3 beta gene expression. These studies showed that the notochord is present in the early nt embryo, but degenerates as development progresses. Overall, these findings support the hypothesis that the notochord plays an active role in left/right patterning. Our results suggest that nt may participate in this process by modulating the notochordal expression of HNF-3 beta.
Melloy
P G
PG
Department of Biology, University of Pennsylvania, Philadelphia 19104, USA.
Ewart
J L
JL
Cohen
M F
MF
Desmond
M E
ME
Kuehn
M R
MR
Lo
C W
CW
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D005314:Embryonic and Fetal Development; D005326:Fetal Proteins; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D006330:Heart Defects, Congenital / Q000196:embryology* / Q000235:genetics; D053823:Hedgehog Proteins; D051542:Hepatocyte Nuclear Factor 3-beta; D055458:Left-Right Determination Factors; D051379:Mice; D009154:Mutation / Q000502:physiology*; D009436:Neural Tube Defects / Q000196:embryology* / Q000235:genetics; D055457:Nodal Protein; D009672:Notochord / Q000196:embryology*; D009687:Nuclear Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D019170:Somites; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D000098908:Brachyury Protein
D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D053823:Hedgehog Proteins; D051542:Hepatocyte Nuclear Factor 3-beta; D055458:Left-Right Determination Factors; D055457:Nodal Protein; D009687:Nuclear Proteins; D011506:Proteins; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000098908:Brachyury Protein; C496503:Foxa2 protein, mouse; C526008:Nodal protein, mouse